In recent years micro chamber and channel structures for performing various reactions and analyses have gained wider use. Examples of scientific fields employing devices comprising such micro channel structures are separation techniques (gas chromatography, electrophoresis), cell biology, DNA sequencing, sample preparation, combinatorial chemistry just to mention a few.
The terms “chamber” and “cavity” will in the context of the invention be used interchangeable if not otherwise specified. A chamber or cavity may be a part of a microchannel.
In certain applications it is common to provide a plurality of micro chambers in which reactions are performed, or in which material is incubated for later use etc. It may often be desirable to move the material from one chamber to another. To this end the chambers are connected by micro channels. Obviously it may become necessary to provide some means of closing said channels after the material has passed therethrough, and also it might be desirable to have the possibility to reopen the channel in order to enable more material to pass through.
In WO 94/29400 there is disclosed a microfabricated channel system. This system is designed for i.a. chemical analytical use, such as electrophoresis and chromatography. In one type of structure a channel and/or cavity system is defined between two plane material layers, the recesses which correspond to the channels and cavities, respectively, being formed in one or both of the opposed layer surfaces. The layers are usually bonded together by gluing.
Alternatively they may be fused together if the two layers consist of thermoplastic material.
In WO 9721090 there is disclosed a microfluidic system having a valve function based on the property of a polymer. Opening of the valve function is actuated by external application of heat. However, the valve function has the drawback that disrupting the heating, e.g. by cooling, will not close the valve.
The type of systems concerned in the present invention may have channels that are of capillary dimensions for liquid flow/transport. The distance between two opposite walls in a channel may be ≦1000 μm, such as ≦100 μm, or even ≦10 μm, such as ≦1 μm. This type of systems may also contain one or more distinct chambers connected to the channels and having volumes being ≦500 μl, such as ≦100 μl and even ≦10 μl such as 1 μl. The depths of the chambers may typically be in the interval ≦1000 μm such as ≦100 μm such as ≦10 μm or even ≦1 μm.
The lower limit for the dimensions is set by manufacturing technology limitations, but can be of the nanometer scale, such as >10 nm, >100 nm or >1000 nm.
One or more liquid transportation systems of this type may be placed on a common plate, for instance rotatable, such as a disc of CD-type. In case of rotatable forms the liquid may be forced through one or more segments of the transportation system by rotating the disc (centripetal force), i.e. the liquid is transported in an outward direction relative the center of the disc. Other types of pressure generating systems may also be used.
A device having one or more liquid transportation system comprising channels and chambers with a depth ≦1000 μm, such as ≦100 μm or even grounder than 10 μm such as ≦1 μm, are further on called a microfabricated device or a micro chamber and channel structure/system or a microfluidic structure/system. The chambers/channels and also the device, structure and system are said to be in the microformat. A microfabricated device typically has its channels and chambers in one plane, such as in the surface of a plate, for instance on a disc. The plate may be circular, oval, rectangular (including in form of a square) or of any other 2D geometric form.
The channels and/or chambers define a flow path pattern in the system, which is delineated by barriers. The barriers can be in form of physical walls, bottoms and tops that are located on or in a planar surface. Hydrophobic barriers combined with aqueous liquids and vice versa for non-polar liquids (see WO 99/58245) have been suggested for defining flow paths and for directing the liquid flow, i.e. to replace the walls and the like in microfabricated devices. There is typically also a second surface applied against the pattern and acting as a top covering the pattern and preventing evaporation of liquid (except for minor parts/dots intended for addition/removal of liquids).
Liquid transportation systems of he type referred to above may also contain valves, pumps, filters and the like.
As mentioned above, in a particular application, a chamber and channel structure is provided in or on a plastic disk. Two or more micro chambers in sequence are aligned radially via a channel. When the disk is spun, material in a chamber located near the center will migrate through the channel to an outwardly located chamber, thereby providing a controllable flow path for reagents to pass from one chamber to another.
However, it is of course difficult to control the flow. The spinning of the disk could be correlated with some position indicating means for locating a sample at a certain point in time, but absent a valve function, there will always be some “spill over” between chambers.
It is known to employ so called stimulus-responsive materials for a number of purposes, e.g. in micro-machines, separation, drug delivery systems etc. This type of material and preparation thereof is discussed in Radiat. Phys. Chem. Vol. 46, No 2, pp185–190, 1995, in an article entitled “Thermo-responsive gels”, by Ichijo et al.
One possible use is an automatic gel valve provided in a tube. A net is attached to cover the outlet of the tube and a porous PVME (poly(vinyl methyl ether)) gel plug is inserted into the tube and positioned on the net. In response to hot water flowing out through the tube, the gel collapses and the hot water was allowed to freely pass through. When cold water is introduced, the gel reversibly regains its swollen state, thereby blocking the outlet. This concept for a valve function is not possible to apply in a multi-valve structure, since only one gel plug can be inserted in a tube in this way. The already introduced plug will hinder the insertion of subsequent plugs downstream. It is also impossible to arrange subsequent plugs upstream of the already positioned plug, since it will be impossible to provide the obstructing net structure for the upstream located plugs.
In U.S. Pat. No. 5,547,472 (Onishi et al) a perforated balloon attached to a catheter was coated with a stimulus-responsive polymer, enabling the pores to be closed or opened in response to e.g. temperature changes. The polymer is bonded to the surface of the balloon and does not appear to be introduced into the pores.
During the priority year, approaches within the same field as the invention have been published by Beebe et al (Nature 404 (Apr. 6, 2000) 588–590), and Liu et al and Madou et al (in Micro Total Analysis System 2000, Ed. Van der Berg et al., Proceedings of the μTAS 2000 Symposium held at Enschede, the Netherlands 14–18 May, 2000, pages 45–48 and 147–150, respectively).